DESCRIPTION (Taken from the application): Osteoporosis is currently a major public health burden and will only increase as the baby boom generation ages. The etiology of osteoporosis is quite complex and is certainly the result of many interacting factors. These factors include: diet and nutrition, environmental insults, medication history, physical activity, gender, ethnic origin, and genetics. The Study of Osteoporotic Fracture (SOF) is a long term prospective study of a female cohort numbering just below 10,000 individuals. Recruitment of women 65 years or older began in 1986 and the women have been followed until the present. The primary focus of SOF has been the epidemiolgy of osteoporotic fractures but a few other conditions are being investigated including osteo arthritis and breast cancer. Early in the study SOF had the foresight to collect blood from participants to use as a source for DNA for future genetic studies. The size and characterization of the SOF cohort make it potentially the premier resource in which to carry out genetic association studies either at the candidate gene level or, as technology progresses, at the whole genome level. The aims of this R03 pilot study grant are geared toward developing the genetic potential of the SOF cohort into a reality. First, DNA will be prepared from all SOF participants that have given their informed consent. This is expected to be roughly 5,000 individuals. The DNA will be extracted from archived blood that was applied to filter paper and stored dry. Since the DNA yield from such samples is relatively small, whole genome preamplification will be applied to increase the number of assays that can be performed. Time will be spent in optimizing protocols so that this valuable resource is used to its fullest. Second, two Single Nucleotide Polymorphism (SNP) assays--TaqMan and array based minisequencing-will be developed and optimized for use with the SOF DNA samples. Finally, a pilot or proof of principle experiment will be carried out which will assay a single candidate gene in all available samples.